Gefitinib-mediated apoptosis is enhanced via inhibition of autophagy by chloroquine diphosphate in cutaneous squamous cell carcinoma cells
Identifieur interne : 000803 ( Main/Exploration ); précédent : 000802; suivant : 000804Gefitinib-mediated apoptosis is enhanced via inhibition of autophagy by chloroquine diphosphate in cutaneous squamous cell carcinoma cells
Auteurs : Jianyu Wang [République populaire de Chine] ; Chaopeng Wang [République populaire de Chine] ; Xia Hu [République populaire de Chine] ; Chang Yu [République populaire de Chine] ; Liang Zhou [République populaire de Chine] ; Zhenhua Ding [République populaire de Chine] ; Meijuan Zhou [République populaire de Chine]Source :
- Oncology Letters [ 1792-1074 ] ; 2019.
Abstract
The development of cutaneous squamous cell carcinoma (cSCC) is associated with activation of the epidermal growth factor receptor (EGFR). EGFR-targeting presents a promising strategy for improving therapeutic efficacy. However, recent studies have suggested that tumours overexpressing EGFR depend on autophagy for survival and exhibit resistance to EGFR-targeting drugs. Chloroquine diphosphate (CQ), an autophagy inhibitor that may enhance the cytocidal effect of gefitinib against cSCC, was used in the present study. Cytotoxicity assays were performed to determine the half-maximal inhibitory concentration values of gefitinib and CQ in A431 cells. Drug interaction was analysed using CompuSyn software, which also determined combination index and dose reduction index values. Apoptosis and autophagy of A431 cells were investigated via flow cytometry, western blotting analyses, acridine orange/ethidium bromide staining and monodansylcadaverine staining. Suppression of autophagy by CQ, which was demonstrated by an alteration in microtubule associated protein 1 light chain 3-B in CQ pre-treated A431 cells, significantly enhanced cell apoptosis, which suggested that gefitinib-induced autophagy is cytoprotective. Thus, CQ was demonstrated to exhibit a synergistic apoptotic effect when used in combination with gefitinib during cSCC therapy. Further
Url:
DOI: 10.3892/ol.2019.10308
PubMed: 31289508
PubMed Central: 6540344
Affiliations:
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China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Department of Radiation Medicine, School of Public Health, Southern Medical University, Guangzhou, Guangdong 510515</wicri:regionArea><wicri:noRegion>Guangdong 510515</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Chaopeng" sort="Wang, Chaopeng" uniqKey="Wang C" first="Chaopeng" last="Wang">Chaopeng Wang</name><affiliation wicri:level="1"><nlm:aff id="af1-ol-0-0-10308">Department of Radiation Medicine, School of Public Health, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Department of Radiation Medicine, School of Public Health, Southern Medical University, Guangzhou, Guangdong 510515</wicri:regionArea><wicri:noRegion>Guangdong 510515</wicri:noRegion></affiliation></author><author><name sortKey="Hu, Xia" sort="Hu, Xia" uniqKey="Hu X" first="Xia" last="Hu">Xia Hu</name><affiliation wicri:level="1"><nlm:aff id="af1-ol-0-0-10308">Department of Radiation Medicine, School of Public Health, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Department of Radiation Medicine, School of Public Health, Southern Medical University, Guangzhou, Guangdong 510515</wicri:regionArea><wicri:noRegion>Guangdong 510515</wicri:noRegion></affiliation></author><author><name sortKey="Yu, Chang" sort="Yu, Chang" uniqKey="Yu C" first="Chang" last="Yu">Chang Yu</name><affiliation wicri:level="1"><nlm:aff id="af1-ol-0-0-10308">Department of Radiation Medicine, School of Public Health, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Department of Radiation Medicine, School of Public Health, Southern Medical University, Guangzhou, Guangdong 510515</wicri:regionArea><wicri:noRegion>Guangdong 510515</wicri:noRegion></affiliation></author><author><name sortKey="Zhou, Liang" sort="Zhou, Liang" uniqKey="Zhou L" first="Liang" last="Zhou">Liang Zhou</name><affiliation wicri:level="1"><nlm:aff id="af1-ol-0-0-10308">Department of Radiation Medicine, School of Public Health, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Department of Radiation Medicine, School of Public Health, Southern Medical University, Guangzhou, Guangdong 510515</wicri:regionArea><wicri:noRegion>Guangdong 510515</wicri:noRegion></affiliation></author><author><name sortKey="Ding, Zhenhua" sort="Ding, Zhenhua" uniqKey="Ding Z" first="Zhenhua" last="Ding">Zhenhua Ding</name><affiliation wicri:level="1"><nlm:aff id="af1-ol-0-0-10308">Department of Radiation Medicine, School of Public Health, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Department of Radiation Medicine, School of Public Health, Southern Medical University, Guangzhou, Guangdong 510515</wicri:regionArea><wicri:noRegion>Guangdong 510515</wicri:noRegion></affiliation></author><author><name sortKey="Zhou, Meijuan" sort="Zhou, Meijuan" uniqKey="Zhou M" first="Meijuan" last="Zhou">Meijuan Zhou</name><affiliation wicri:level="1"><nlm:aff id="af1-ol-0-0-10308">Department of Radiation Medicine, School of Public Health, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Department of Radiation Medicine, School of Public Health, Southern Medical University, Guangzhou, Guangdong 510515</wicri:regionArea><wicri:noRegion>Guangdong 510515</wicri:noRegion></affiliation></author></analytic><series><title level="j">Oncology Letters</title><idno type="ISSN">1792-1074</idno><idno type="eISSN">1792-1082</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The development of cutaneous squamous cell carcinoma (cSCC) is associated with activation of the epidermal growth factor receptor (EGFR). EGFR-targeting presents a promising strategy for improving therapeutic efficacy. However, recent studies have suggested that tumours overexpressing EGFR depend on autophagy for survival and exhibit resistance to EGFR-targeting drugs. Chloroquine diphosphate (CQ), an autophagy inhibitor that may enhance the cytocidal effect of gefitinib against cSCC, was used in the present study. Cytotoxicity assays were performed to determine the half-maximal inhibitory concentration values of gefitinib and CQ in A431 cells. Drug interaction was analysed using CompuSyn software, which also determined combination index and dose reduction index values. Apoptosis and autophagy of A431 cells were investigated via flow cytometry, western blotting analyses, acridine orange/ethidium bromide staining and monodansylcadaverine staining. Suppression of autophagy by CQ, which was demonstrated by an alteration in microtubule associated protein 1 light chain 3-B in CQ pre-treated A431 cells, significantly enhanced cell apoptosis, which suggested that gefitinib-induced autophagy is cytoprotective. Thus, CQ was demonstrated to exhibit a synergistic apoptotic effect when used in combination with gefitinib during cSCC therapy. Further <italic>in vivo</italic> investigations are required to confirm the results of the present study.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Stratigos, A" uniqKey="Stratigos A">A Stratigos</name></author><author><name sortKey="Garbe, C" uniqKey="Garbe C">C Garbe</name></author><author><name sortKey="Lebbe, C" uniqKey="Lebbe C">C Lebbe</name></author><author><name sortKey="Malvehy, J" uniqKey="Malvehy J">J Malvehy</name></author><author><name sortKey="Del Marmol, V" uniqKey="Del Marmol V">V del Marmol</name></author><author><name sortKey="Pehamberger, H" uniqKey="Pehamberger H">H Pehamberger</name></author><author><name sortKey="Peris, K" uniqKey="Peris K">K Peris</name></author><author><name sortKey="Becker, Jc" uniqKey="Becker J">JC Becker</name></author><author><name sortKey="Zalaudek, I" uniqKey="Zalaudek I">I Zalaudek</name></author><author><name sortKey="Saiag, P" uniqKey="Saiag P">P 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Wong</name></author><author><name sortKey="Kapanen, Ai" uniqKey="Kapanen A">AI Kapanen</name></author><author><name sortKey="Rawji, Js" uniqKey="Rawji J">JS Rawji</name></author><author><name sortKey="Warburton, C" uniqKey="Warburton C">C Warburton</name></author><author><name sortKey="Qadir, Ma" uniqKey="Qadir M">MA Qadir</name></author><author><name sortKey="Donohue, E" uniqKey="Donohue E">E Donohue</name></author><author><name sortKey="Roberge, M" uniqKey="Roberge M">M Roberge</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Wang, Jianyu" sort="Wang, Jianyu" uniqKey="Wang J" first="Jianyu" last="Wang">Jianyu Wang</name></noRegion><name sortKey="Ding, Zhenhua" sort="Ding, Zhenhua" uniqKey="Ding Z" first="Zhenhua" last="Ding">Zhenhua Ding</name><name sortKey="Hu, Xia" sort="Hu, Xia" uniqKey="Hu X" first="Xia" last="Hu">Xia Hu</name><name sortKey="Wang, Chaopeng" sort="Wang, Chaopeng" uniqKey="Wang C" first="Chaopeng" last="Wang">Chaopeng Wang</name><name sortKey="Yu, Chang" sort="Yu, Chang" uniqKey="Yu C" first="Chang" last="Yu">Chang Yu</name><name sortKey="Zhou, Liang" sort="Zhou, Liang" uniqKey="Zhou L" first="Liang" last="Zhou">Liang Zhou</name><name sortKey="Zhou, Meijuan" sort="Zhou, Meijuan" uniqKey="Zhou M" first="Meijuan" last="Zhou">Meijuan Zhou</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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